Lysosomal Acid Lipase Deficiency -Another Needle in a Haystack

A recent article (Atherosclerosis 2014; 235: 21-30) reviews lysosomal acid lipase deficiency (LAL-D) and how this rare disease needs to be considered by pediatric hepatologists.

LAL-D is a rare lysosomal storage disease which encompasses a rapidly progressive disease in infants (previously referred to as Wolman disease) as well as a later-onset condition called cholesteryl ester storage disease (CESD).  Both of these diseases are caused by mutations in the LIPA gene and share the same pathophysiology related to deficiency of LAL. The disease prevalence estimates vary widely (1 in 40,000 to 1 in 300,000) and depend on ethnicity and location.  Jewish, Iraqi, and Iranian infants appear to be at highest risk.

According to the review algorithm, patients with three or more of the following should be considered for screening:

  • ALT >1.5 ULN
  • Hepatomegaly (may be mild)
  • HDL <50 mg/dL
  • Low BMI (in adults <30 kg/m2)
  • Liver biopsy with microvesicular steatosis; grossly the liver may appear orange

Thus, the potential target patients:

  1. Non-obese individuals with persistent increases in LFTs –usually with LDL >160 and low HDL <50
  2. Non-obese NAFLD/microvesicular steatosis

Given the potential for treatment with recombinant sebelipase alfa (Synageva Biopharma) and the widely available testing, looking for LAL-D makes sense in selected patients; though, even in highly selected patients, finding cases may truly be like finding the so-called ‘needle in a haystack’ given the huge numbers of individuals with elevated ALTs who do not have LAL-D.

Note: many of the review’s authors received research grants from Synageva.  (I do not have any financial conflicts to disclose.)

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